SCH532706

A 'second-generation' small molecule CCR5 antagonist, SCH532706, boosted with ritonavir, demonstrated potent anti-HIV activity and was generally well-tolerated in a small ten-day monotherapy study according to data presented in early 2008.¹

The drug was being developed by Schering-Plough but its future is uncertain following the company's acquisition by Merck and the termination of the development of vicriviroc, a first-generation CCR5 inhibitor also developed by Schering-Plough. In the study, 60mg twice-daily SCH532706 boosted with ritonavir was given to four treatment-naive participants and eight ART-experienced participants who had been off therapy for at least three months. After ten days of therapy, the mean HIV viral load was reduced over one log and in all participants, HIV remained CCR5-tropic. At day 20, viral load was still about 1 log below the baseline level, though it returned to the initial level by day 25.

Although eleven of the twelve participants reported at least one treatment-emergent adverse event, most commonly gastrointestinal upset, 75% of these were considered mild and over half were thought to be unrelated to the study drug.

There was one serious adverse event, moderate pericarditis (inflammation of the sac that surrounds the heart), that was classified as “possibly related” to SCH532706 because the investigators could not identify any other cause. This occurred 13 days after the last dose of the study drug.

Further studies will go forward using the drug dosed once daily given its long half-life (just under 40 hours). Earlier test-tube studies found that SCH532706 had high potency against 30 different HIV-1 isolates. The drug appeared safe in a previous small study of healthy HIV-negative volunteers.